Rapid mitogen-activated protein kinase activation by transforming growth factor α in wounded rat intestinal epithelial cells

M. Goke, M. Kanai, K. Lynch-Devaney, D. K. Podolsky

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Abstract

Background and Aims: To define signaling events initiating healing after intestinal epithelial injury, activation of mitogen-activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. Methods: Proteins isolated from wounded monolayers of nontransformed intestinal epithelial cells (IEC-6) were analyzed for tyrosine phosphorylation and MAPK expression by Western blot. Extracellular signal-regulated kinase (ERK) 1, ERK2, and Raf-1 activities were assessed by immune complex kinase assays. Results: Tyrosine phosphorylation of several proteins including ERK1 was substantially increased 5 minutes after injury. Another MAPK, c-Jun-N- terminal protein kinase (JNK), was also activated after wounding. Conditioned medium from wounded but not intact IEC-6 monolayers resulted in increased activity of ERK1, ERK2, and Raf-1 kinase. Wound-conditioned medium stimulated proliferation of subconfluent IEC-6 cells compared with conditioned medium from intact IEC-6 cultures and contained higher amounts of transforming growth factor (TGF)-α than supernatants of confluent IEC-6 cultures. Activation of ERK1 and ERK2 was partially inhibited by neutralizing anti- TGF-α. Conclusions: Wounding of intestinal epithelial cells results in activation of Raf-1, ERK1, ERK2, and JNK1 MAPKs and subsequent cell proliferation in vitro. Activation of ERK1 and ERK2 is mediated in part by TGF-α.

Original languageEnglish (US)
Pages (from-to)697-705
Number of pages9
JournalGastroenterology
Volume114
Issue number4 I
DOIs
StatePublished - Jan 1 1998

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ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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